PMID- 9832923
OWN - NLM
STAT- MEDLINE
DCOM- 19981229
LR  - 20191210
IS  - 0955-8810 (Print)
IS  - 0955-8810 (Linking)
VI  - 9
IP  - 5-6
DP  - 1998 Sep
TI  - The discriminative stimulus effects of clomethiazole in the rat.
PG  - 379-88
AB  - Rats were trained in a two-lever drug discrimination procedure using saline or 
      clomethiazole (8 mg/kg, s.c. 15 min) as the training stimuli. A criterion of 9/10 
      days correct lever choice was adopted to select rats for substitution tests. The 
      clomethiazole (CMZ) cue was not especially strong, and stable performance at this 
      level was not achieved consistently. Nevertheless, in a series of substitution 
      tests carried out in extinction, diazepam (3 mg/kg), chlordiazepoxide (10 mg/kg), 
      phenobarbital (60 mg/kg), dizocilpine (0.1 mg/kg) and mianserin (3.0 mg/kg) were 
      found to substitute for the training dose of CMZ. The first two of these produced 
      a percentage choice of the drug lever equal to that produced by the training dose 
      of CMZ (full generalization) whereas the latter three produced only partial 
      generalization. Ethanol, muscimol, allopregnanolone, chlorpromazine and 
      amitriptyline did not generalize to CMZ. CMZ is known to potentiate 
      gamma-aminobutyric acid (GABAA) receptor function, a finding supported by the 
      generalization to CMZ of the two benzodiazepines and phenobarbital. However, not 
      all drugs acting at GABAA receptors generalized to CMZ. Although CMZ has no 
      affinity for the N-methyl-D-aspartate (NMDA) receptor, it antagonizes a number of 
      pharmacological responses mediated by NMDA receptors. The generalization in the 
      drug discrimination procedure reported here support the suggestion that altering 
      GABA activity can modulate NMDA-mediated responses. The lack of generalization 
      after treatment with ethanol, chlorpromazine and amitriptyline suggests that the 
      interoceptive cues are not mediated by a generalized sedation or drug-induced 
      motor impairment.
FAU - Evenden, J
AU  - Evenden J
AD  - Department of Pharmacology, Preclinical Research and Development, Astra Arcus AB, 
      Sodertalje, Sweden.
FAU - Ensler, K
AU  - Ensler K
FAU - Jackson, D M
AU  - Jackson DM
FAU - Stephan-Dahlin, C
AU  - Stephan-Dahlin C
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Behav Pharmacol
JT  - Behavioural pharmacology
JID - 9013016
RN  - 0 (Anti-Anxiety Agents)
RN  - 0 (Antidepressive Agents, Tricyclic)
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (GABA Agents)
RN  - 0 (Hypnotics and Sedatives)
RN  - 0 (Neuroprotective Agents)
RN  - 0C5DBZ19HV (Chlormethiazole)
RN  - Q3JTX2Q7TU (Diazepam)
SB  - IM
MH  - Animals
MH  - Anti-Anxiety Agents/pharmacology
MH  - Antidepressive Agents, Tricyclic/pharmacology
MH  - Antipsychotic Agents/pharmacology
MH  - Central Nervous System Depressants/pharmacology
MH  - Chlormethiazole/*pharmacology
MH  - Cues
MH  - Diazepam/pharmacology
MH  - Discrimination Learning/drug effects
MH  - Discrimination, Psychological/*drug effects
MH  - GABA Agents/pharmacology
MH  - Hypnotics and Sedatives/pharmacology
MH  - Male
MH  - Neuroprotective Agents/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reinforcement Schedule
EDAT- 1998/12/02 00:00
MHDA- 1998/12/02 00:01
CRDT- 1998/12/02 00:00
PHST- 1998/12/02 00:00 [pubmed]
PHST- 1998/12/02 00:01 [medline]
PHST- 1998/12/02 00:00 [entrez]
AID - 10.1097/00008877-199809000-00001 [doi]
PST - ppublish
SO  - Behav Pharmacol. 1998 Sep;9(5-6):379-88. doi: 10.1097/00008877-199809000-00001.